Manufacturers Back Innovation Initiatives

Amidst the clamor to curb the cost and time of drug development and thus speed more new products to patients, policymakers are devising "pro-innovative" approaches for testing and regulating medical products. Some of these proposals may be included in the user-fee legislation moving forward on Capitol Hill, along with provisions to ensure drug safety and help FDA contend with an increasingly global marketplace. In addition, several Obama administration initiatives offer support for biomedical innovation as part of broader economic and regulatory programs.

Public-private collaboration

After a year of discussion about doing more to translate biomedical discoveries into effective therapies, National Institutes of Health (NIH) Director Francis Collins is moving forward with his collaborative effort to "repurpose" old drugs sitting on manufacturers' shelves. US Health and Human Services (HHS) Secretary Kathleen Sebelius joined Collins and three leading pharmaceutical companies last month to announce a pilot program to uncover new uses for abandoned compounds.

The new National Center for Advancing Translational Sciences (NCATS) is linking up with Pfizer, AstraZeneca, and Eli Lilly to support independent studies on about 20 drugs that the companies previously developed but never brought to market. NIH will provide $20 million in grants next year to fund promising research proposals, along with templates for agreements on dealing with intellectual property. The manufacturers will provide researchers with the compounds and relevant data, while retaining rights to their products, Collins explained. Researchers from academia, nonprofits, and biotech companies will be able to publish study results and negotiate licenses on new discoveries. The research agreement templates are key to speeding up negotiations among all parties and making the program work. NIH intentionally ruled out seeking additional uses for approved drugs, as those raise more complex IP issues.

NIH is soliciting comments on the templates and plans to publish the list of compounds available for research in a few months in an effort to award initial grants by spring 2013. Manufacturers view the NIH program as a way to extend the kinds of arrangements they already have with individual research institutes, including AstraZeneca's partnership with the United Kingdom's Medical Research Program. The selected compounds have been tested for safety in early clinical trials, but lacked sufficiently robust results to support larger studies. The hope is that these abandoned products will do better with new targets and new indications.

Public–private partnerships to repurpose approved drugs is one item in the national "Bioeconomy Blueprint" from the White House Office of Science and Technology Policy (OSTP), which maps out opportunities to promote economic growth and improve public health through biotech innovation. This grab-bag of ideas also cites research to support pluripotent cell technology and collaborations to validate promising drug targets and develop standards that can improve protein manufacturing processes. The report calls for FDA to use its vast repository of clinical-drug safety and efficacy data to speed drug development and envisions harnessing biology as a manufacturing platform for rapid production of new high-value materials, medicines, devices, and fuels.

Adding to PDUFA

New drug development also may benefit from a number of measures before Congress that aim to speed up regulatory review and eliminate hurdles to market approval. These measures have been proposed as additions to legislation reauthorizing the Prescription Drug User Fee Act (PDUFA) and several other new and old FDA user-fee programs; there's pressure to get the bill done before the end of June.

The basic PDUFA agreement negotiated by FDA and industry last year includes provisions encouraging research on new treatments for rare diseases and identifying new biomarkers and research tools able to streamline clinical studies. FDA would approve more applications in the first review cycle through greater interaction with sponsors during the review process. An important, but less noticed, item sets the stage for manufacturers to file applications for new drugs and biologics in a common, electronic format within five years.

In addition to the agreed-on PDUFA plan, a host of additional legislative "enhancements" to the bill aim to make the regulatory process more efficient and predictable. The Senate Health, Education, Labor, and Pensions Committee approved its Food and Drug Safety and Innovation Act (FDASIA) in April, but acknowledged that it still needs to resolve several issues related to innovation and supply-chain security before the bill comes up for vote by the full Senate. The House negotiated a similar but slightly different measure a few weeks later. Debate continues over incentives for manufacturers to develop new antibiotics and added leverage for FDA to use priority review and fast-track approval strategies to speed new treatments to market. Industry also would like more flexibility for scientific experts with ties to industry to serve on FDA advisory committees. Both manufacturers and patient advocates want to expand FDA's use of the accelerated-approval process, and the agency agrees to some extent.

At the April annual meeting of the Food and Drug Law Institute (FDLI), FDA Commissioner Margaret Hamburg voiced support for legislative language that would provide "clarity to industry and the public" on the use of accelerated approval for "a wide variety of diseases and conditions, including rare diseases." Hamburg also backed proposals to codify the concept of "breakthrough drugs"—that is, products that elicit such a dramatic response in early clinical trials that they warrant market approval based on limited clinical evidence.

Yet, Hamburg doesn't want overly proscriptive legislation. She said nothing about appointing an FDA "chief innovation officer" with authority to ensure that reviewers accept data from unconventional clinical research programs previously okayed by the agency. FDA also opposes industry's proposal to expand the agency's mission statement from "promoting the public health" to include "spurring economic growth." Agency officials say it's impossible to calculate how approval or rejection of a new drug or medical device would affect jobs and growth, as one sponsor might gain from approval, but a competitor could lose.